Risk of Four Geriatric Syndromes: A Comparison of Mental Health Care and General Hospital Inpatients.

An observational, cross-sectional study is conducted to compare elevated risk scores of four geriatric syndromes (falls, malnutrition, physical impairment, delirium) in older hospitalized psychiatric patients (n=178) with patients hospitalized in a general hospital (n=687). The median age of all patients was 78 years (IQR 73.3-83.3), 53% were female. After correction for age and gender, we found significantly more often an elevated risk in the mental health care group, compared to the general hospital group of falls (Odds Ratio (OR) = 1.75; 95% Confidence Interval (CI) 1.18-2.57), malnutrition (OR = 4.12; 95% CI 2.67-6.36) and delirium (OR = 6.45; 95% CI 4.23-9.85). The risk on physical impairment was not statistically significantly different in both groups (OR = 1.36; 95% CI .90-2.07). Older mental health care patients have a higher risk to develop geriatric syndromes compared to general hospital patients with the same age and gender, which might be explained by a higher level of frailty.

[Psychiatric symptoms and COVID-19: results of a national case register]. / Psychiatrische symptomen en COVID-19: resultaten uit een landelijk register.

BACKGROUND: Psychiatric disorders are associated with a more severe course of COVID-19. COVID-19 can also lead to psychiatric symptoms. AIM: To gain insight into vulnerabilities and protective factors for the course of COVID-19 in a Dutch (neuro)psychiatric population. METHOD: Patients were divided into three groups: patients with pre-existent mental disorders without and with new (neuro)psychiatric symptoms (NPS) during COVID-19 and patients without pre-existent mental disorders who developed de novo NPS during COVID-19. We summarize the characteristics of each group and compare the subgroups with inferential statistics. RESULTS: 186 patients were included in the case register. Patients with NPS showed a more severe course of COVID-19. Mortality in patients with NPS was higher in patients with pre-existent mental disorders compared to patients without pre-existent mental disorders. The most frequently reported de novo psychiatric symptoms during COVID-19 were delirium (46-70%), anxiety (53-54%) and insomnia (18-42%). CONCLUSION: NPS might be an expression of a more severe COVID-19 episode. In patients who developed NPS during COVID-19 we found evidence for a higher mortality risk in patients with pre-existent mental disorders. Extra vigilance for neuropsychiatric symptoms during COVID-19 is warranted.

ECT non-remitters: prognosis and treatment after 12 unilateral electroconvulsive therapy sessions for major depression.

BACKGROUND: Depressive disorder causes significant suffering in patients and caregivers worldwide. Electroconvulsive therapy (ECT) is a highly effective antidepressant treatment, but little is known about the prognosis and treatment of patients who do not achieve remission with ECT. We investigated prognosis and treatment of patients with major depression who did not achieve remission after 12 unilateral electroconvulsive therapy sessions. METHODS: We conducted a retrospective, naturalistic follow-up study. Patients who had previously participated in a double-blind randomized controlled trial that compared brief pulse with ultra-brief pulse ECT and who had not achieved remission after 12 right unilateral (RUL) ECT sessions were selected for this study. We analysed the type of treatments received during the 6-month follow-up and studied the occurrence of remission and response. The primary outcome was remission, defined as a Montgomery-Åsberg Depression Rating Scale score <10. RESULTS: Eighty-one patients were randomized, of which 18 patients did not remit. Eight of these non-remitters achieved remission during follow-up (44.4%) while 7 did not achieve remission (38.9%). Remission data could not be retrieved for 3 patients (16.7%). Remission was achieved in 6 patients by a combination of continuing unilateral ECT with antidepressants or switching to bilateral ECT. LIMITATIONS: This is a retrospective study with only a small number of patients. Treatment after RUL ECT non-remission was not standardized. CONCLUSION: When patients with major depression do not achieve remission after 12 RUL ECT sessions, they have still a reasonable chance of remission within 6 months. Continuing ECT has the best chance of success.

[ResPECT - a decade of Flemish-Dutch ECT research]. / ResPECT ­ een decennium Vlaams-Nederlands onderzoek naar elektroconvulsietherapie.

BACKGROUND: There is increasing clinical and scientific interest in electroconvulsive therapy (ECT). AIM: To provide an overview of the main research findings of the Flemish-Dutch research consortium ResPECT. METHOD: We report on our review of the relevant literature. RESULTS: Our studies confirm that ECT is one of the most efficient treatments for depression in later life and for depression with psychotic features. Older people with age-related brain pathology can respond well to ECT. It is still preferable to apply a standard pulse-width because this increases the efficacy of the treatment and minimises the cognitive impact. Even vulnerable older people can react favourably to ECT. CONCLUSION: Recent findings of the ResPECT consortium are providing new insights that are applicable in daily clinical practice. Research into mechanisms of action can also increase our understanding of the pathophysiology of severe depression.

Screening of Autism Spectrum Disorders in Geriatric Psychiatry.

Autism spectrum disorders (ASD) are difficult to detect in old age. This study examined if ASD symptoms in older adults (age > 60) can be detected with the Dutch informant personality questionnaire, (Hetero-Anamnestische Persoonlijkheidsvragenlijst, HAP) in a mental health setting. Patients with ASD (N = 40) were compared to patients with a different psychiatric diagnosis (N = 43; personality disorders excluded). The ASD group had significant higher scores on the scales 'Socially avoidant behavior', 'Rigid behavior' and 'Unpredictable and impulsive behavior'. These scales were able to discriminate between individuals with or without ASD. The HAP can thus be used as a screening instrument for ASD symptoms in elderly patients. Further research is needed to clarify what items have the best predictive validity for ASD symptoms.

Prevalence of mild cognitive impairment and dementia in older non-western immigrants in the Netherlands: a cross-sectional study.

OBJECTIVE: In the Netherlands, persons of Turkish, Moroccan and Surinamese descent form the largest groups of non-western immigrants. A high prevalence of mild cognitive impairment (MCI) and dementia has been described in immigrant populations in the United States of America and the United Kingdom. We determined the prevalence of MCI and dementia in older community-dwelling adults from the largest non-western immigrant groups in the Netherlands. METHODS: Participants, aged 55 years and older, of Turkish, Moroccan (Arabic or Berber), Surinamese (Creole or Hindustani) or Dutch descent were recruited via their general practitioners. Cognitive deficits were assessed using the Cross-Cultural Dementia screening instrument, which was validated in poorly educated people from different cultures. Differences in prevalence rates of MCI and dementia between the immigrant groups and a native Dutch group were analysed using chi-square tests. RESULTS: We included 2254 participants. Their mean age was 65.0 years (standard deviation, 7.5), and 44.4% were male. The prevalence of MCI was 13.0% in Turkish, 10.1% in Moroccan-Arabic, 9.4% in Moroccan-Berber and 11.9% in Surinamese-Hindustani participants, compared to 5.9% in Surinamese-Creoles and 3.3% in native Dutch. The prevalence of dementia was 14.8% in Turkish, 12.2% in Moroccan Arabic, 11.3% in Moroccan Berber and 12.6% in Surinamese-Hindustani participants, compared to 4.0% in Surinamese-Creoles and 3.5% in native Dutch. CONCLUSIONS: MCI and dementia were three to four times more prevalent in the majority of non-western immigrant groups when compared to the native Dutch population. These differences are important for planning and improving healthcare facilities. Copyright © 2016 John Wiley & Sons, Ltd.

Depression in later life: a more somatic presentation?

BACKGROUND: Depression later in life may have a more somatic presentation compared with depression earlier in life due to chronic somatic disease and increasing age. This study examines the influence of the presence of chronic somatic diseases and increasing age on symptom dimensions of late-life depression. METHODS: Baseline data of 429 depressed and non-depressed older persons (aged 60-93 years) in the Netherlands Study of Depression in Old Age were used, including symptom dimension scores as assessed with the mood, somatic and motivation subscales of the Inventory of Depressive Symptomatology-Self Report (IDS-SR). Linear regression was performed to investigate the effect of chronic somatic diseases and age on the IDS-SR subscale scores. RESULTS: In depressed older persons a higher somatic disease burden was associated with higher scores on the mood subscale (B = 2.02, p = 0.001), whereas higher age was associated with lower scores on the mood (B = -2.30, p < 0.001) and motivation (B = -1.01, p = 0.006) subscales. In depressed compared with non-depressed persons, a higher somatic disease burden showed no different association with higher scores on the somatic subscale (F(1,12) = 9.2; p = 0.003; partial η(2)=0.022). LIMITATIONS: Because the IDS-SR subscales are specific for old age, it was not feasible to include persons aged < 60 years to investigate differences between earlier and later life. CONCLUSIONS: It seems that neither higher somatic disease burden nor higher age contributes to more severe somatic symptoms in late-life depression. In older old persons aged ≥ 70 years, late-life depression may not be adequately recognized because they may show less mood and motivational symptoms compared with younger old persons.

The subscale structure of the Inventory of Depressive Symptomatology Self Report (IDS-SR) in older persons.

BACKGROUND: Using symptom dimensions may be more effective than using categorical subtypes when investigating clinical outcome and underlying mechanisms of late-life depression. Therefore, this study aims to identify both the factor and subscale structure of late-life depression underlying the Inventory of Depressive Symptomatology Self Report (IDS-SR) in older persons. METHOD: IDS-SR data of 423 participants in the Netherlands Study of Depression in Older Persons (NESDO) were analyzed by exploratory (EFA) and confirmatory factor analysis (CFA). The best-fitting factor solution in a group of older persons with a major depressive disorder diagnosis in the last month (n = 229) was replicated in a control group of older persons with no or less severe depression (n = 194). Multiple group (MG-CFA) was performed to evaluate generalizability of the best-fitting factor solution across subgroups, and internal consistency coefficients were calculated for each factor. RESULTS: EFA and CFA show that a 3-factor model fits best to the data [comparative fit index (CFI) = 0.98; Tucker Lewis Index (TLI) = 0.99; and root mean square error of approximation (RMSEA) = 0.052], consisting of a 'mood', 'motivation' and 'somatic' factor with adequate internal consistencies (alpha coefficient 0.93, 0.83 and 0.70, respectively). MG-CFA shows a structurally similar factor model across subgroups. CONCLUSION: The IDS-SR can be used to measure three homogeneous symptom dimensions that are specific to older people. Application of these dimensions that may serve as subscales of the IDS-SR may benefit both clinical practice and scientific research.

Phenomenology of depression in older compared with younger adults: meta-analysis.

BACKGROUND: Late-life depression may differ from early-life depression in its phenomenology. AIMS: To investigate the effect of age on the phenomenology of major depression. METHOD: A systematic search was conducted in PubMed, Embase and PsycINFO for all studies examining the relation between age and phenomenology of major depression according to RDC, DSM and ICD criteria. Studies were included only if the age groups were compared at the single-item level using the 17-, 21- or 24-item versions of the Hamilton Rating Scale for Depression; a meta-analysis was done for each item of the 17-item scale. RESULTS: Eleven papers met the inclusion criteria. Older depressed adults, compared with younger depressed adults, demonstrated more agitation, hypochondriasis and general as well as gastrointestinal somatic symptoms, but less guilt and loss of sexual interest. CONCLUSIONS: The phenomenology of late-life depression differs only in part from that of early-life depression. Major depression in older people may have a more somatic presentation, whereas feelings of guilt and loss of sexual function may be more prevalent in younger people.

Outcome of late-life depression after 3 years of sequential treatment.

OBJECTIVE: To study the outcome of a sequential treatment protocol in elderly, severely depressed in-patients. METHOD: All 81 patients from a 12-week double-blind randomized controlled trial (RCT) comparing venlafaxine with nortriptyline were asked to participate in a 3 year follow-up study. Thirty-two patients who did not achieve remission during the RCT, entered an open sequential treatment protocol and were treated with augmentation with lithium, switch to a monoamine oxidase inhibitor or ECT. RESULTS: Seventy-eight of the 81 patients (96.3%) achieved a response [> or = 50% reduction in Montgomery Asberg Depression Rating Scale score) and 68 patients (84%) a complete remission (final MADRS score < or = 10) within 3 years of treatment. Greater severity and longer duration of the depressive episode at baseline predicted poor recovery. Augmentation with lithium may be the best treatment option in treatment resistant depressed elderly. Only few patients dropped-out due to side-effects. CONCLUSION: Our study demonstrates the importance of persisting with antidepressant treatment in elderly patients who do not respond to the first or second treatment.

[Frontal syndrome. A patient with a recognisable clinical picture but without a clear aetiology. A case study]. / Het frontaal syndroom: een patiënt met een herkenbaar klinisch beeld maar zonder duidelijke etiologie.

A 63-year-old man presented with behavioural disturbances but had no problems with memory or orientation. We diagnosed a frontal syndrome and we describe the symptoms and the differential diagnosis. The precise aetiology remains unclear, although an infarction of the nucleus caudatus is suspected.

Cellular folate vitamer distribution during and after correction of vitamin B12 deficiency: a case for the methylfolate trap.

Haematological sequellae of vitamin B12 deficiency are attributed to disturbed DNA synthesis, but vitamin B12 itself plays no role in DNA biosynthesis. A proposed explanation for this is the methylfolate trap hypothesis. This hypothesis states that B12 deficiency impairs overall folate metabolism because 5-methyltetrahydrofolate (5MTHF) becomes metabolically trapped. This trap results from the fact that 5MTHF can neither be metabolised via the methionine synthase pathway, nor can it be reconverted to its precursor, methylenetetrahydrofolate. Other manifestations of the methylfolate trap include cellular folate loss because of shorter 5MTHF polyglutamate chains and global hypomethylation. The methylfolate trap has never been demonstrated in humans. We describe a patient with B12 deficiency who was homozygous for the common methylenetetrahydrofolate reductase (MTHFR) C677T mutation. We analysed red blood cell (RBC) folate vitamers and global DNA methylation by liquid chromatography (LC) in combination with tandem mass spectrometry, and 5MTHF polyglutamate length by LC-electrochemical detection. Compared to post-B12 supplementation values, homocysteine was higher (52.9 micromol/l vs. 16.8 micromol/l), RBC folate was lower (268.92 nmol/l vs. 501.2 nmol/l), the 5MTHF fraction of RBC folate was much higher (94.5% vs. 67.4%), polyglutamate chain length was shorter (more tetra- and pentaglutamates), and global DNA methylation was 22% lower. This is the first time that virtually all features of the methylfolate trap hypothesis have been demonstrated in a human with vitamin B12 deficiency.

[6S]5-methyltetrahydrofolate or folic acid supplementation and absorption and initial elimination of folate in young and middle-aged adults.

OBJECTIVES: To assess the effects of supplementation with the diastereoisomer of 5-methyltetrahydrofolate ([6S]5-methylTHF), as an alternative supplement for folic acid, on folate absorption and elimination, in two age groups. DESIGN: A randomized, double-blind intervention study. SUBJECTS: A total of 12 young (<30 y) and 12 middle-aged (> or =50 y) healthy volunteers were recruited. METHODS: Volunteers were randomized to receive daily supplementation with 400 mug folic acid or equimolar amounts of [6S]5-methylTHF during 5 weeks. Before and after supplementation, absorption and initial elimination were calculated following oral [(2)H(2)]folic acid test doses using isotope kinetics in plasma. RESULTS: Folic acid absorption was lower in the middle-aged as compared to the young adults, both before (P = 0.03) and after (P = 0.05) supplementation. In the young adults, absorption decreased by 22% after [6S]5-methylTHF and increased by 21% after folic acid (P = 0.02). In the other age group, no such changes were found. The folate rate constant of elimination increased after folic acid supplementation in the young (+50%; P = 0.05) but not in the middle-aged (+18%; P = 0.5) adults. CONCLUSIONS: Young adults show increased folate turnover after folic acid supplementation relative to the effect of [6S]5-methylTHF supplementation. Similar differences are not observed in middle-aged adults, in whom folic acid absorption was found to be lower as compared to the young adults. SPONSORSHIP: Financial support was received from the European Union 5th Framework Programme (Grant QLRT-1999-00576).

[Psychic consequences on the elderly of sexual abuse in their youth]. / Psychische gevolgen op oudere leeftijd van seksueel misbruik in de jeugd.

Three women, aged 64, 65 and 60 years, who were admitted for psychopathology revealed for the first time that they had been sexually abused as a child by a relative. The first woman sought help following the death of her husband, the second after her daughter was raped, and the third suffered from increasing cognitive impairment. Through therapy, they learned how to process their history of incest. In psychiatric patients, the prevalence of sexual abuse in their youth varies from 5-45% in different studies, depending on the definition of sexual abuse. Two Dutch studies of elderly psychiatric inpatients found a prevalence of 16% sexual abuse in 32 male and female patients and 8% in 110 female patients, respectively. Sexual abuse may have a great, lifelong impact on the victims. Many psychiatric and psychological consequences are found in adult populations, but no study has yet included the elderly. All clinicians should be aware that signs and symptoms in the elderly might be related to sexual abuse.

5-Methyltetrahydrofolic acid and folic acid measured in plasma with liquid chromatography tandem mass spectrometry: applications to folate absorption and metabolism.

We describe a liquid chromatography (LC) tandem mass spectrometry (MS-MS) method for the determination of 5-methyltetrahydrofolic acid (5-methylTHF) and folic acid concentrations and enrichments in human plasma. It was used to study absorption and initial metabolism in five volunteers with two simultaneously administered oral test doses ([(13)C(6)]folic acid in capsules and [(2)H(2)]folic acid in a drink). [(13)C(5)]5-methylTHF and [(2)H(4)]folic acid were used as internal standards. Plasma samples (2 ml) were purified using folate binding protein affinity columns, followed by a concentration step. After LC separation, folates were detected using positive electrospray ionization MS-MS under multiple reaction monitoring conditions. Calibrations were linear for 5-methylTHF over the range 1.2 x 10(-11) (=limit of detection) to 3.2 x 10(-7)mol/L and for folic acid over the range 5 x 10(-10) (=limit of detection) to 4.5 x 10(-8)mol/L. For 5-methylTHF concentration in plasma, intraassay coefficient of variation was within 8.6% (and for unlabeled 5-methylTHF it was within 2.8%) and interassay coefficient of variation was within 9.0%. For folic acid concentrations these coefficient of variations were within 7.5% and within 6.5%, respectively. The [(13)C(6)] and [(2)H(2)] isotopomers of folic acid and 5-methylTHF were measured in the plasma of each volunteer for 8h. After accounting for the time delay due to capsule opening, the modeling results showed no significant differences in absorption time, first pass effect, and elimination rate in the folic acid test doses in capsule or drink. We conclude that LC-MS-MS offers increased sensitivity for quantification of plasma concentrations and enrichments of 5-methylTHF and folic acid and is applicable to stable-isotope studies in humans.

Determination of 13C and 15N enrichments of urea in plasma by gas chromatography-combustion isotope ratio mass spectrometry and gas chromatography-mass spectrometry using the 2-methoxypyrimidine derivative.

We describe a GC-MS and GC-c-IRMS method for the determination of labeled urea tracer enrichments in plasma as a result of combined 13C- and 15N(2)-urea infusion experiments in piglets. Urea was converted into 2-methoxypyrimidine, a stable derivative, suited for analyses by both GC-MS and GC-c-IRMS. Using calibration curves for the respective working ranges (13C-urea: 0-1% APE; 15N(2)-urea: 0-7% MPE) enrichments were established in single point measurements; for 15N(2)-urea as values+/-0.15% MPE (95% confidence interval); for 13C-urea as values+/-0.02% APE (95% confidence interval). 15N(1)-urea enrichments were determined by measurement of the same sample with GC-c-IRMS and GC-MS. Subtraction of the 13C specific GC-c-IRMS data from the nondiscriminating GC-MS data for the sum of 13C- and 15N(1)-urea resulted in 15N(1)-urea enrichments+/-0.15% MPE (95% confidence interval). Application of the method in a combined 13C-urea bolus and 15N(2)-urea primed constant infusion experiment in piglet was demonstrated.

Determination of isotopic enrichments of [1-13C]homocysteine, [1-13C]methionine and [2H3-methyl-1-13C]methionine in human plasma by gas chromatography-negative chemical ionization mass spectrometry.

We describe a reliable method for the simultaneous determination of isotopic enrichments of [1-13C]homocysteine, [1-13C]methionine and [2H3-methyl-1-13C]methionine in human plasma. Accurate [1-13C]homocysteine calibration standards were prepared by chemical conversion via thiolactonisation of [1-13C]methionine standards. Based upon anion-exchange chromatography, (di)acetyl-3,5-bis-trifluoromethylbenzyl derivatives, preparation of accurate calibration curves and gas chromatography-negative chemical ionization mass spectrometry, isotopic enrichments in human plasma could be determined with TTR (%) <+/-0.2% (N=3) for [1-13C]homocysteine (enrichment range 0-8%), [1-13C]methionine (enrichment range 0-3%) and [2H3-methyl-1-13C]methionine (enrichment range 0-12%). The method was applied in a [2H3-methyl-1-13C]methionine tracer infusion study in a biological model.

Methylmalonic semialdehyde dehydrogenase deficiency: psychomotor delay and methylmalonic aciduria without metabolic decompensation.

A patient presenting with developmental delay but no episodes of metabolic acidosis was found to excrete significant amounts of methylmalonate (MMA) without any associated increased excretion of malonate, ethylmalonate, 3-hydroxypropionate, or beta-alanine. In contrast to patients with methylmalonic aciduria due to deficient mutase or impaired cobalamin metabolism, there was no increase of propionylcarnitine in blood or urine. The activity of methylmalonyl-CoA mutase and the pathway for cobalamin metabolism were also intact. The quantitative levels of the various labeled enantiomers of 3-hydroxyisobutyric (3-HIBA), 3-aminoisobutyric (3-AIBA), MMA, and propionylcarnitine were compared following separate intravenous infusions of equimolar doses of [2H8]-valine or [2H4]thymine in this patient and another with methylmalonyl-CoA mutase deficiency. Levels of labeled S- and R-3-HIBA and S- and R-3-AIBA indicated an isolated defect in methylmalonic semialdehyde dehydrogenase in this patient. This condition can be recognized by plasma MMA levels of approximately 8.5 microM (cf. 400 microM in mutase deficiency), urine MMA of 20-55 micromol/kg/24 h (cf. 1150 micromol/kg/24 h), no increase in propionylcarnitine following an oral carnitine load, and increased excretion of S-3-AIBA-nearly 10 times that observed in mutase deficiency. The ratio of R-AIBA to S-AIBA of <1 also reflects this disorder.

Phytanic acid and pristanic acid are oxidized by sequential peroxisomal and mitochondrial reactions in cultured fibroblasts.

The relationship between peroxisomal and mitochondrial oxidation of the methyl branched fatty acids, phytanic acid and pristanic acid, was studied in normal and mutant human skin fibroblasts with established enzyme deficiencies. Tandem mass spectrometry was used for analysis of the acylcarnitine intermediates. In normal cells, 4,8-dimethylnonanoylcarnitine (C11:0) and 2,6-dimethylheptanoylcarnitine (C9:0) accumulated after incubation with either phytanic acid or pristanic acid. These intermediates were not observed when peroxisome-deficient cells from Zellweger patients were incubated with the same compounds, pointing to the involvement of peroxisomes in the formation of these acylcarnitine intermediates. Similar experiments with fibroblasts deficient in carnitine palmitoyltransferase I, carnitine-acylcarnitine translocase or carnitine palmitoyltransferase II revealed that mitochondrial carnitine palmitoyltransferase I is not required for the oxidation of phytanic acid or pristanic acid, whereas both carnitine-acylcarnitine translocase and carnitine palmitoyltransferase II are necessary. These studies demonstrate that both phytanic acid and pristanic acid are initially oxidized in peroxisomes to 4,8-dimethylnonanoyl-CoA, which is converted to the corresponding acylcarnitine (presumably by peroxisomal carnitine octanoyltransferase), and exported to the mitochondrion. After transport across the mitochondrial membrane and transfer of the acylgroup to coenzyme A, further oxidation to 2,6-dimethylheptanoyl-CoA occurs.